Coronary artery disease (CAD), also named ischemic heart disease, involves the atherosclerosis of artery supplying heart muscle, which is caused by vascular stenosis or plaque rupture and occlusion accompanying myocardial ischemia, hypoxia or necrosis. The disease can lead to a series of serious cardiovascular problems such as angina and myocardial infarction. CAD remains one of the main killers to human health with high morbidity, high disability rate, high recurrence rate, high mortality, and multiple comorbidities and thus it has been one of the main diseases threatening human health.
Based on pathophysiologic mechanisms, CAD is currently divided into stable coronary artery disease (i.e., stable angina pectoris, SA) and acute coronary syndrome (ACS). ACS is further divided into unstable angina pectoris (UA) and acute myocardial infarction (AMI). The emergence and progression of CAD are as follows: normal coronary artery (NCA), coronary atherosclerosis (CA), SA, UA, and AMI.
Coronary artery atherosclerosis is the main cause and early stage of CAD. Coronary atherosclerosis is a common progressive arterial disease. The lesions are mainly involved in the medium sized muscular arteries with arterial intimal lipid deposition and proliferation of smooth muscle cells, which can lead to the formation of local plaque and make the arteries hard. When the plaque ruptures, thrombosis, embolism and hemorrhage happen and lead to partial or complete occlusion of the involved arteries. They are seen as the complications of atherosclerosis clinically. Early stage of coronary artery atherosclerosis may emerge before 10 years old while it takes 20 to 30 years to form artery stenosis. Because of non-obvious clinical symptoms of atherosclerosis in early stage, it is not easy to be noticed or regarded. Therefore, the early prevention and diagnosis of coronary artery atherosclerosis can effectively prevent the occurrence of CAD.
Coronary angiography can accurately determine the degree of stenosis of coronary artery and it is the “gold standard” for diagnosis of CAD (research on the differences in clinical diagnosis of coronary heart disease by using coronary angiography gold standards and conventional diagnosis techniques, Shu Rongwen, et. al., Journal of Navy Medicine, 2015, 4). Unfortunately, the invasive coronary angiography based on intervention surgery is costly and can simply determine the degree of stenosis of coronary artery. Moreover, Doctors need to refer to the patients' electrocardiogram, echocardiography, treadmill exercise test, CT and other test results to make the final diagnosis, which may cause erroneous diagnosis or missed diagnosis because of subjective judgment of doctors or patients' unclear statement. This affects the prognosis of the patients a lot. To reduce the threat to patients' life and improve their life quality a cheap, non-invasive and simple diagnostic method with high diagnostic accuracy is urgently needed.
Metabolomics, as an important part of system biology, focuses on endogenous metabolites in organism and their changes with internal and external factors. It can analyze body fluids quickly and non-invasively such as blood and urine, and obtain the metabolites that indicate the various biochemical reactions from the differences in metabolic profiles. The commonly used analytical techniques currently include nuclear magnetic resonance (NMR), mass spectrometry (LC-MS/GC-MS) and so on. Because of the simplicity in sample preparation, high sensitivity and wide linear range, LC-MS/GC-MS is becoming a more and more commonly used technology in metabolomics investigations. Plasma analysis is a common diagnostic method in clinical and is widely used because of its simplicity, low cost, and relatively non-invasiveness.
Up to now, no studies on plasma metabolomic profiling for characterizing different types of CAD were reported. Plasma metabolomic profiling of people with normal coronary artery and patients with coronary artery atherosclerosis and various types of CAD is of high meaning for clinical diagnosis of CAD and differentiation of the various types of CAD in early stage.